Together, our data suggested that treatment of CFF‐1 inhibited PI3K/AKT pathway and activated FOXO1, and finally activated both intrinsic and extrinsic apoptosis pathways (Caspase dependent) in prostate cancer cells; the CFF‐1‐induced PCa cell apoptosis was p53‐independent. The gene discussed is TP53; the disease is prostate carcinoma.